Transcript Chapter 8

Structures and Structure
Descriptions
Chapter 8 Protein Bioinformatics
Protein Classes
1. Active – Mobility and catalysis
–
soluble and globular in shape
2. Passive – structural
3. Membrane – control import and
export through membrane
Folding in Globular Proteins
• fold into compact units
• 100-1000 nucleotides
• Stable fold has minimum energy
– Native state
• Energy loss occurs when bonds are formed:
– H-Bonds
– disulfide bridges (cysteine)
– metallic bonds w/ metal ions
Folding
Formation of H-bonds:
• Hydrophilic amino acids are soluble,
hydrophobic are not
• To maximize H-bonds, put hydrophilic on
the surface so the whole protein is soluble
• Causes the formation of the two dominant
Secondary Structure Elements (SSEs):
1. α-helix
2. β-strand
Structural Comparison
• Fine Level (residue)
– used for finding spatial similarities – active and
binding sites
– helpful for determining function
– done by specifying coordinates, distances, or
torsion angles
• Coarse Level (SSE)
– used for comparing on the global level
– helpful for classifying proteins into classes
– done by describing SSEs using line segments or as
ellipsoids
Process
Structure Description
• Architecture (or Geometry)
position of
elements
(atoms or residues)
• Topology -
order of elements along
the backbone
• Properties - physio-chemical properties
and types of SSEs
Coordinates
From NMR or X-Ray Crystallography
ATOM
ATOM
ATOM
ATOM
ATOM
ATOM
ATOM
ATOM
ATOM
ATOM
ATOM
ATOM
1
2
3
4
5
6
7
8
9
10
11
12
N
CA
C
O
CB
CG
CD
N
CA
C
O
CB
PRO
PRO
PRO
PRO
PRO
PRO
PRO
TYR
TYR
TYR
TYR
TYR
A
A
A
A
A
A
A
A
A
A
A
A
2
2
2
2
2
2
2
3
3
3
3
3
31.242
31.195
29.975
29.727
31.063
30.276
30.829
29.189
28.011
26.711
26.629
28.055
3.064
2.392
2.923
4.132
0.905
0.947
2.121
2.020
2.405
1.995
0.949
1.772
39.284
37.963
37.197
37.181
38.251
39.549
40.343
36.613
35.850
36.517
37.161
34.459
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
39.90
31.96
30.23
27.03
36.57
35.11
42.06
22.83
18.42
19.46
24.89
17.73
N
C
C
O
C
C
C
N
C
C
O
C
Distance Matrices
• Distances can be stored with 3n-6
distances instead of 4n-10 coordinates.
• 2D representation of the 3D structure
Torsion Angles
• Angles between two bonds
of each atom in the
backbone are approx. equal
• Freedom comes in rotating
around single bonds
(-70,-20), (-72,60), (-70,120), (-60,170), (-65, 125),
(-100, 45), (-100, -65), (-105, -66), (-100, 60)
Line Segments (sticks)
• Fit a line to the Catom of each residue
by least squares
Ellipsoids
• Three inertial axes
long axis corresponds to stick representation
Helices
• Formed by HBonds between
residues in the
same helix
• α-helix
310-helix
π-helix
4-turn helix, min. 4 residues
3-turn helix, min. 3 residues
5-turn helix, min. 5 residues
Strands and Sheets
• Formed by successive HBonds between residues can
be far apart in sequence.
Cartoons for Secondary
Structure Elements (SSE)
• Topology of Protein Structure (TOPS)
– Triangular symbols represent beta strands
– Circular symbols represent helices (alpha and 310)
– The peptide chain is divided into a number of
fragments each labelled with an integer (i),
beginning at Ni and ending at Ci+1.
– The first fragment is N1->C2 (or N->C).
– Each fragment lies in only one structural domain.
– Where the chain crosses between domains it leaves
the first at Ci and joins the next at Ni.
– Each secondary structure element has a direction (N
to C) which is either "up" ( out of the plane of the
diagram ) or "down" (into the plane of the diagram).
Comparing Structures
• Structure Representations – pg. 185-186
(11-12 of pdf)
– Strings
– List of unit descriptions
– Set of unit descriptions
– Graphs
– Feature Arrays
Pairwise Comparison
• Finding equivalence or alignment giving
highest score is NP-Complete
Example
• Alignment
– ACSL-DRTS-IRV
– A-TLREKSSLIR-
• Know first 5 residues
– ACSL-D
– A-TLRE
But not so with structures
highest score alignment
of entire structures
highest score alignment
of first five residues
Last Slide 
• Explore pdb and install cn3d
• http://www.rcsb.org/pdb
• http://www.ncbi.nlm.nih.gov/Structure/
CN3D/cn3d.shtml
RCSB PDB - HUMAN GLUTATHIONE S-TRANSFERASE